Objectives: 1) Possible role of psychosine (galactosylsphingosine) in the pathogenesis of globoid cell leukodystrophy (Krabbe's disease, GLD) will be explored by investigating it effects on in vitro galactocerebroside synthesis, on organotypic CNS cultures, and on intact brains. Search for psychosine or its derivatives in GLD tissues, and for existence of galactocerebroside acyl hydrolase in normal brain will be initiated. 2) Cerebroside metabolism in GLD will be studied in the canine GLD and CNS explants. The experiments with dogs involve in vivo injection of isotopic galactose and sulfate, followed by determination of their incorporation into cerebroside and sulfatide in the brain and kidney. 3). Sphingolipid Beta-glactosidases will be purified and characterized. The major interest is the interrelationship among the specific sphingolipid Beta-galactosidases and between them and the nonspeciffic 4-methylumbelliferyl Beta-galactosidase. Attempts will be made to isolate mutant "enzymes" from genetic sphingolipidoses for further characterization. 4) The distribution of lipid glycosidases in different brain cell types will be studied. 5) The use of cultured fibroblasts as the primary tool to study metabolic neurological disorders will be explored.